There is increasing evidence that the potent tumor promoting phorbol esters may resemble the prostaglandin hormones or act in part to lead to the synthesis of prostaglandin endoperoxides and the reactive intermediates such as the short-lived thromboxane A2. It is important, in these investigator's view, that structure-activity relationships for tumor promoting phorbol esters be correlated with initial cell membrane reactions such as changes in ion transport and the subsequent metabolism events, and that these be compared with prostaglandins, particularly prostaglandin F2alpha. Since TPA also shares properties common to the Ca2 ion ionophore A23187 (e.g. both cause release of arachidonate from membrane phospholipids resulting in the synthesis of reactive prostaglandin intermediates, both induce platelet aggregation and both stimulate mitogenesis of human peripheral lymphocytes as does prostaglandin F2alpha) it is of interest to establish what specific dynamic changes in Ca2 ion movements are elicited by phorbol esters (and secondarily by prostaglandins). Since we have observed that cellular Ca2 ion homeostasis involves at least four stages of Ca2 ion movements, it will be necessary to examine each step to analyze phorbol ester effects. It appears important to establish whether changes in Ca2 ion movements are a primary or secondary action of tumor promoting phorbol esters. This will require the use of rapid kinetic measurements under varied conditions, e.g. at 0 degrees where Ca2 ion efflux is minimal, and/or also the presence of selected inhibitors of mitochondrial energy generation.